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Background Acute arterial mesenteric ischemia requires emergency treatment and is associated with high mortality rate and poor quality of life. Identifying factors associated with survival without intestinal resection (hereafter, intestinal resection-free [IRF] survival) could help in treatment decision-making after first-line endovascular revascularization. Purpose To identify factors associated with 30-day IRF survival in patients with acute arterial mesenteric ischemia whose first-line treatment was endovascular revascularization. Materials and Methods Patients with acute arterial mesenteric ischemia whose first-line treatment was endovascular revascularization because of a low probability of bowel necrosis were included in this single-center retrospective cohort (May 2014 to August 2022). Patient demographics, laboratory values, clinical characteristics at admission, CT scans, angiograms, and endovascular revascularization-related variables were included. The primary end point was 30-day IRF survival, and secondary end points were 3-month, 1-year, and 3-year overall survival. Factors independently associated with 30-day IRF survival were identified with binary logistic regression. Results A total of 117 patients (median age, 70 years [IQR, 60-77]; 53 female, 64 male) were included. Within 30 days after revascularization, 73 of 117 patients (62%) survived without resection, 28 of 117 (24%) survived after resection, 14 of 117 (12%) died without resection, and two of 117 (2%) underwent resection but died. The 30-day IRF survival was 63% (74 of 117). The 3-month, 1-year, and 3-year mortality rate was 18% (21 of 117), 21% (25 of 117), and 27% (32 of 117), respectively. Independent predictors of 30-day IRF survival were persistent bowel enhancement at initial CT (odds ratio [OR], 0.3; 95% CI: 0.2, 0.8; P = .013) and C-reactive protein (CRP) level less than 100 mg/L (OR, 0.3; 95% CI: 0.1, 0.8; P = .002). The 30-day IRF survival was 86%, 61%, 47%, and 23% in patients with both favorable features, persistent bowel enhancement but CRP level greater than 100 mg/L, no bowel enhancement but CRP level less than 100 mg/L, and both unfavorable features, respectively. Conclusion Independent predictors associated with 30-day IRF survival in patients with acute arterial mesenteric ischemia whose first-line treatment was endovascular revascularization were persistent bowel wall enhancement at initial CT and CRP level less than 100 mg/L. © RSNA, 2024 Supplemental material is available for this article.
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Procedimentos Endovasculares , Isquemia Mesentérica , Humanos , Masculino , Feminino , Isquemia Mesentérica/cirurgia , Isquemia Mesentérica/diagnóstico por imagem , Isquemia Mesentérica/mortalidade , Procedimentos Endovasculares/métodos , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Intestinos/irrigação sanguínea , Intestinos/diagnóstico por imagem , Intestinos/cirurgia , Doença AgudaRESUMO
Bone marrow smear showing histiocytes (black arrow) containing sea blue granules stained with May-Grünwald Giemsa.
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Pancitopenia , Síndrome do Histiócito Azul-Marinho , Humanos , Pancitopenia/etiologia , Nutrição Parenteral/efeitos adversos , HistiócitosRESUMO
PURPOSE: Hyper activation of the JAK-STAT signaling underlies the pathophysiology of many human immune-mediated diseases. Herein, the study of 2 adult patients with SOCS1 haploinsufficiency illustrates the severe and pleomorphic consequences of its impaired regulation in the intestinal tract. METHODS: Two unrelated adult patients presented with gastrointestinal manifestations, one with Crohn's disease-like ileo-colic inflammation refractory to anti-TNF and the other with lymphocytic leiomyositis causing severe chronic intestinal pseudo-occlusion. Next-generation sequencing was used to identify the underlying monogenic defect. One patient received anti-IL-12/IL-23 treatment while the other received the JAK1 inhibitor, ruxolitinib. Peripheral blood, intestinal tissues, and serum samples were analyzed before-and-after JAK1 inhibitor therapy using mass cytometry, histology, transcriptomic, and Olink assay. RESULTS: Novel germline loss-of-function variants in SOCS1 were identified in both patients. The patient with Crohn-like disease achieved clinical remission with anti-IL-12/IL-23 treatment. In the second patient with lymphocytic leiomyositis, ruxolitinib induced rapid resolution of the obstructive symptoms, significant decrease of the CD8+ T lymphocyte muscular infiltrate, and normalization of serum and intestinal cytokines. Decreased frequencies of circulating Treg cells, MAIT cells, and NK cells, with altered CD56bright:CD16lo:CD16hi NK subtype ratios were not modified by ruxolitinib. CONCLUSION: SOCS1 haploinsufficiency can result in a broad spectrum of intestinal manifestations and need to be considered as differential diagnosis in cases of severe treatment-refractory enteropathies, including the rare condition of lymphocytic leiomyositis. This provides the rationale for genetic screening and considering JAK inhibitors in such cases.
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Haploinsuficiência , Inibidores do Fator de Necrose Tumoral , Adulto , Humanos , Proteínas Supressoras da Sinalização de Citocina/genética , Interleucina-12 , Interleucina-23 , Proteína 1 Supressora da Sinalização de Citocina/genéticaRESUMO
Eosinophilic inflammation of the digestive tract is an inflammatory disease characterized by extensive infiltration of eosinophils into the gastrointestinal tract. It can be either a primary disorder of the digestive tract or be secondary to another cause of tissue eosinophilia. Primary disorders include eosinophilic esophagitis (OE) and eosinophilic gastroenteritis (GEEo). These are 2 rare pathologies considered to be diseases related to a Th2-mediated food allergy. The role of the pathologist is twofold: (1) he must make the diagnosis of tissue esosinophilia and propose the various causes, knowing that a secondary cause is the most frequently observed; (2) identify the abnormal number of polymorphonuclear eosinophils, which implies knowing the normal distribution of eosinophils in the different digestive segments. To carry the diagnosis of EO, the threshold of polymorphonuclear eosinophils must be ≥ 15/fields × 400. There is no predefined threshold concerning the other segments of the digestive tract to carry the diagnosis of GEEO. In addition, to make the diagnosis of primary digestive tissue eosinophilia, the patient must be symptomatic with histological evidence of eosinophilia and have ruled out all secondary causes. The main differential diagnosis of OE is gastroesophageal reflux disease. The differential diagnoses of GEEo are multiple, including primarily drugs and parasitic infections.
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Eosinofilia , Gastroenterite , Masculino , Humanos , Eosinofilia/diagnóstico , Eosinofilia/etiologia , Eosinofilia/patologia , Gastroenterite/complicações , Gastroenterite/diagnóstico , Inflamação/complicaçõesRESUMO
OBJECTIVES: This study aimed to investigate the prevalence, risk factors, and outcomes of colonic involvement in patients with acute mesenteric ischemia (AMI). METHODS: CT scans from a prospective cohort of 114 AMI patients treated in an intestinal stroke center between 2009 and 2018 were blindly reviewed by two radiologists. Colon involvement was defined on CT scan by the presence of at least one of the following CT colonic features: wall thickening, pneumatosis, decreased wall enhancement, dilatation, or perforation. In addition, the clinical, biological, and radiological characteristics of patients with and without colonic involvement were compared to identify risk factors for colonic involvement on CT and its impact on morbidity and mortality. RESULTS: Colonic involvement was identified in 32/114 (28%) patients with AMI, the right colon being more frequently involved (n = 29/32, 91%). Wall thickening (n = 27/32) was the most common CT finding. Occlusion of the inferior mesenteric artery was the only statistically significant risk factor for colonic involvement (35% vs. 15%, p = 0.02). Patients with colonic involvement on CT vs. those without had more frequently transmural colonic necrosis (13% vs. 0%, p = 0.006), short bowel syndrome (16% vs. 4%, p = 0.04), need for long-term parenteral support (19% vs. 5%, p = 0.03), and death during follow-up (22% vs. 10%, p = 0.03). DISCUSSION: In patients with AMI, colonic involvement is associated with increased morbidity and mortality and should be carefully searched for during initial CT scan assessment. KEY POINTS: ⢠In a prospective cohort of acute mesenteric ischemia patients from an intestinal stroke center, 28% had an associated colonic involvement on CT. ⢠Colonic involvement on CT most commonly affected the right colon, and the occlusion of the inferior mesenteric artery was the only risk factor. ⢠Colonic involvement on CT was associated with increased morbidity and mortality and should be carefully searched for during initial CT scan assessment.
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Isquemia Mesentérica , Colo/diagnóstico por imagem , Humanos , Isquemia/diagnóstico por imagem , Isquemia/epidemiologia , Isquemia Mesentérica/complicações , Isquemia Mesentérica/diagnóstico por imagem , Isquemia Mesentérica/epidemiologia , Prevalência , Estudos Prospectivos , Estudos Retrospectivos , Fatores de RiscoRESUMO
Fistulizing anoperineal lesions are severe complications of Crohn's disease (CD) that affect quality of life with a long-term risk of anal sphincter destruction, incontinence, permanent stoma, and anal cancer. Despite several surgical procedures, they relapse in about two-thirds of patients, mandating innovative treatments. Ultrasmall particles of iron oxide (USPIO) have been described to achieve in vivo rapid healing of deep wounds in the skin and liver of rats thanks to their nanobridging capability that could be adapted to fistula treatment. Our main purpose was to highlight preclinical data with USPIO for the treatment of perianal fistulizing CD. Twenty male Sprague Dawley rats with severe 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced proctitis were operated to generate two perianal fistulas per rat. At day 35, two inflammatory fistulas were obtained per rat and perineal magnetic resonance imaging (MRI) was performed. After a baseline MRI, a fistula tract was randomly drawn and topically treated either with saline or with USPIO for 1 min (n = 17 for each). The rats underwent a perineal MRI on postoperative days (POD) 1, 4, and 7 and were sacrificed for pathological examination. The primary outcome was the filling or closure of the fistula tract, including the external or internal openings. USPIO treatment allowed the closure and/or filling of all the treated fistulas from its application until POD 7 in comparison with the control fistulas (23%). The treatment with USPIO was safe, permanently closed the fistula along its entire length, including internal and external orifices, and paved new avenues for the treatment of perianal fistulizing Crohn's disease.
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Doença de Crohn , Fístula Retal , Animais , Masculino , Ratos , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Doença de Crohn/patologia , Nanopartículas Magnéticas de Óxido de Ferro , Recidiva Local de Neoplasia , Qualidade de Vida , Ratos Sprague-Dawley , Fístula Retal/tratamento farmacológico , Fístula Retal/etiologia , Resultado do TratamentoRESUMO
Glomus tumors (GTs) are perivascular tumors mostly occurring in the distal extremities. Rare cases arise in the digestive tract and may be misdiagnosed with neuroendocrine or gastrointestinal stromal tumors. We aimed to specify the features of GT of the upper digestive tract. Clinical, histological, phenotypic, and molecular features of 16 digestive GTs were analyzed, of whom two underwent whole exome and RNA sequencing to search for gene alterations. RNA-sequencing disclosed a t(1:5)(p13;q32) translocation, which resulted in the fusion of CARMN and NOTCH2 in two GTs. The fusion gene encoded a protein sequence corresponding to the NOTCH2 intracellular domain that functions as transcription factor. These finding was supported by high expression of genes targeted by NOTCH. The CARMN-NOTCH2 translocation was detected in 14 out of 16 (88%) GTs of the upper digestive tract; but in only in two out of six cutaneous GTs (33%). Most digestive GT arose from the stomach (n = 13), and the others from duodenal (2) or oesophagous (1). Nuclear expression of NOTCH2 was detected in the 14 cases containing the fusion transcripts. The CARMN-NOTCH2 fusion transcript may contribute to activation of the NOTCH2 pathway in GT and drive tumor development. The high frequency of this translocation in GT of the upper digestive track suggest that detection of nuclear NOTCH2 expression may be useful diagnostic biomarker of these tumors.
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Biomarcadores Tumorais/genética , Neoplasias Gastrointestinais/genética , Fusão Gênica , Tumor Glômico/genética , MicroRNAs/genética , Receptor Notch2/genética , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/patologia , Tumor Glômico/metabolismo , Tumor Glômico/patologia , HumanosRESUMO
CONTEXT: The origin of tumor deposit in colorectal cancer is still unknown, and currently there is no single morphological feature to distinguish a metastatic lymph node from a tumor deposit. Histologically, the normal lymph node capsule and trabeculae contain a smooth muscular layer, which when present in extramural deposits would strongly suggest their lymph node origin. OBJECTIVE: We analyze the value of the smooth muscular layer criterion in reclassifying tumor deposit into metastatic lymph node. DESIGN: A total of 458 colo-rectal carcinomas surgical specimens treated or not by neoadjuvant (radio)chemotherapy were retrospectively included. Harvested tumor deposits were analyzed by Hematoxylin and Eosin and elastin staining on 10 consecutive serial sections and by α- smooth muscle actin immunostaining. RESULTS: A total of 129 tumor deposits were identified. 77 (60%) tumor deposits were reclassified into metastatic lymph node, of which 63 (49%) presented a smooth muscular layer on the initial Hematein Eosin staining and/or after serial tissue sections, confirmed by positive α-smooth muscle actin immunostaining in 43 out of 45 cases (90%). Fourteen (18%) additional tumor deposits were reclassified into metastatic lymph node by the appearance of lymphoid tissue after serial sections. CONCLUSIONS: The presence of a smooth muscular layer in a presumable tumor deposit is helpful in pointing out its lymph node origin in patients with colo-rectal carcinomas. This criterion could improve the inter-observer agreement of tumor deposit identification, allowing accurate nodal staging and better assessment of patient's prognosis.
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Colo/patologia , Linfonodos/patologia , Metástase Linfática/patologia , Neoplasias Retais/patologia , Adenocarcinoma/patologia , Adulto , Idoso , Humanos , Excisão de Linfonodo/métodos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/diagnósticoRESUMO
INTRODUCTION: The department of neuropathology of Sainte-Anne Hospital uses zinc-formalin as the fixative agent for its samples. No publication referenced in Pubmed has proven the validity of this fixative agent. In the context of the accreditation of our standard staining (HPS for Hemalun-Phloxin-Saffron), we started a file for the validation of this method in which the fixative agent constitutes an « interfering ¼ substance which can modify the quality of the technique. The aim of this study was to prove that the use of zinc-formalin as a fixative agent is as suitable as the fixation with 4 % buffered formalin. MATERIALS AND METHODS: A cohort of samples fixed by zinc-formalin and by 4 % buffered formalin was performed on fresh samples, then cut and stained by HPS. The slides were interpreted by three pathologists (one of them was outside our centre) ``blind '' to the fixative agent and they evaluated four criteria (general quality of the staining, components of the extracellular matrix, cytoplasmic details, and nuclear details) and scored them (from 0 to 3) according to the Association française en assurance qualité (AFAQAP) recommendations. RESULTS: The cohort included 43 samples. The results of the analysis showed that for samples fixed by zinc-formalin, three of the four criteria obtained significantly a better score than the samples fixed by classical formalin. DISCUSSION AND CONCLUSIONS: Our results show that the zinc-formalin fixative does not constitute an ``interfering '' agent for the quality of the HPS staining for neuropathological samples.
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Formaldeído , Zinco , Fixadores , Humanos , Coloração e Rotulagem , Fixação de TecidosRESUMO
BACKGROUND AND AIMS: Different types of histologic lesions at the ileal margin, detected by histology, have been associated with increased rates of recurrence after ileocaecal surgery in patients with Crohn's disease (CD). We aimed to characterize histologic features of the ileal margin and to evaluate their association with disease recurrence. METHODS: We collected histologic data from 211 patients with ileal or ileocolonic CD who underwent ileocolonic resections at hospitals in France from September 2010 through December 2016. Ileal margins were analyzed. Early endoscopic recurrence was defined by a Rutgeerts score of i2 or more, 6 months after surgery. We also collected data from 10 adults with healthy ileum who underwent ileocecal resection for colonic tumors (controls). Clinical relapse was defined by CD-related symptoms confirmed by imaging, endoscopy, therapy intensification, CD-related complication, or subsequent surgery. RESULTS: Six months after surgery, 49% of patients had endoscopic recurrence; 5 years after surgery, 57% of patients had clinical relapse. Ileal margins were macroscopically affected in 20.9% of patients. CD transmural lesions at the margin (defined by mucosal ulceration or cryptitis, submucosal fibrosis and lymphoplasmacytic infiltrate of the subserosa) were observed in 13.6% of patients. Endoscopic recurrence was observed in 75% of patients with CD transmural lesions vs 46% of patients without (P =.005). In multivariate analysis, CD transmural lesions at the margin were independently associated with early endoscopic recurrence (OR, 3.83; 95% CI, 1.47-11.05; P =.008) and clinical recurrence (OR 2.04; 95% CI, 1.09-3.99; P =.026). CONCLUSION: In patients with CD, transmural lesions at the ileal margin were associated with an increased risk of post-operative recurrence. Histologic features of the ileal margin should be included in making decisions about post-operative therapy.
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Doença de Crohn/patologia , Doença de Crohn/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Íleo , Margens de Excisão , Adulto , Anastomose Cirúrgica/efeitos adversos , Colectomia/efeitos adversos , Colectomia/métodos , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Feminino , Humanos , Íleo/patologia , Íleo/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RecidivaRESUMO
INTRODUCTION: To investigate the factors associated with a delayed diagnosis (DD) of acute mesenteric ischemia (AMI). METHODS: An observational cohort study from an intestinal failure center. The primary outcome was DD >24 hours. RESULTS: Between 2006 and 2015, 74 patients with AMI were included and 39 (53%) had a DD. Plasma lactate <2 mmol/L (odd ratio: 3.2; 95% confidence interval: 1.1-9.1; P = 0.03) and unenhanced computed tomography scan (odds ratio: 5.9; 95% confidence interval: 1.4-25.8; P = 0.01) were independently associated with DD. DISCUSSION: Suspicion of AMI should no longer be affected by normal plasma lactate levels and should prompt evaluation by a contrast-enhanced computed tomography-scan.
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Meios de Contraste , Diagnóstico Tardio/estatística & dados numéricos , Ácido Láctico/sangue , Isquemia Mesentérica/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Dor Abdominal/fisiopatologia , Doença Aguda , Adulto , Anastomose Cirúrgica , Doença Crônica , Estudos de Coortes , Colo/cirurgia , Diagnóstico Precoce , Intervenção Médica Precoce , Feminino , Humanos , Intestino Delgado/cirurgia , Jejunostomia , Masculino , Isquemia Mesentérica/sangue , Isquemia Mesentérica/fisiopatologia , Isquemia Mesentérica/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Síndrome do Intestino Curto , Vômito/fisiopatologiaRESUMO
Hepatic veno-occlusive disease (HVOD), alias sinusoidal obstruction syndrome, may develop as a complication of chemotherapy in the setting of hematopoietic stem cell transplantation. HVOD is less frequently described after exposure to chemotherapy in the nontransplant setting and can also be a complication after ingestion of toxins, such as pyrrolizidine alkaloids. Veno-occlusive disease may also affect the lungs, and it is therefore termed pulmonary veno-occlusive disease (PVOD). Similarly, PVOD can develop after exposure to chemotherapeutic agents in the treatment of solid and hematological malignancies. In addition, PVOD has also been linked to autoimmune disorders and occupational solvent exposure. Finally, the heritable form of PVOD is due to biallelic mutations of the EIF2AK4 gene. Both HVOD and PVOD share common histopathological features and pathophysiologic mechanisms. Both clinical disorders are rare complications that can appear after exposure to the common inciting trigger of chemotherapeutic agents. The present review aims to summarize the current knowledge of HVOD and PVOD and to describe both similarities as well as differences regarding both conditions.
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Hepatopatia Veno-Oclusiva/patologia , Pneumopatia Veno-Oclusiva/patologia , Animais , Diagnóstico Diferencial , Modelos Animais de Doenças , Predisposição Genética para Doença , Hepatopatia Veno-Oclusiva/diagnóstico , Hepatopatia Veno-Oclusiva/etiologia , Hepatopatia Veno-Oclusiva/terapia , Humanos , Prognóstico , Pneumopatia Veno-Oclusiva/diagnóstico , Pneumopatia Veno-Oclusiva/etiologia , Pneumopatia Veno-Oclusiva/terapia , Ratos , Fatores de RiscoRESUMO
INTRODUCTION: Surgery is required in patients with symptoms of chronic radiation-induced enteritis (CRE) resistant to medical therapy. The study aimed to correlate histopathologic features of CRE to the clinical presentation and the postoperative recurrence. MATERIAL AND METHOD: All patients with small bowel resection performed for CRE between 2006 and 2017 were studied. Histological data were retrospectively correlated to initial clinical data and to postoperative recurrence of CRE (occlusion, need for parenteral nutrition) observed during a median follow-up of 32 months. RESULTS: Forty-one patients were studied (39 women and 2 men, median age 62 yo at time of radiation for pelvic cancer, 80% gynecologic). Median time to surgery after radiation was 3 years. Ileocaecal resections (80% of patients) removed 60cm (median length). Histologically, a diffuse obliterative arteriopathy was present in 24 (59%) patients, highly associated to amyotrophy, villous atrophy and ulceration observed in 66, 63 and 34% of patients respectively (P<.05). Diffuse arteriopathy was uncorrelated with patient's age and vascular risk factor (tobacco, diabetes, hypertension, dyslipidemia). Median time to surgery after radiation was longer in patients presenting with obliterative arteriopathy (13 years vs. 2.6 years, P=0.0002). During follow-up, half of the patients had a recurrence of CRE, uncorrelated to the arteriopathy. CONCLUSION: Radiation-induced enteritis requiring late surgery after radiation presented histologically with a diffuse obliterative arteriopathy and ischemic features. In our center, half of the patients were cured by surgery. The arterial injury was not a risk factor for postoperative recurrence.
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Enterite , Lesões por Radiação , Enterite/etiologia , Enterite/terapia , Feminino , Humanos , Intestino Delgado , Masculino , Pessoa de Meia-Idade , Nutrição Parenteral , Lesões por Radiação/patologia , Lesões por Radiação/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND & AIMS: It remains unclear whether the classic imaging criteria for the non-invasive diagnosis of hepatocellular carcinoma (HCC) can be applied to chronic vascular liver diseases, such as Budd-Chiari syndrome (BCS). Herein, we aimed to evaluate the diagnostic value of washout for the discrimination between benign and malignant lesions in patients with BCS. METHODS: This retrospective study included all patients admitted to our institution with a diagnosis of BCS and focal lesions on MRI from 2000 to 2016. MRI images were reviewed by 2 radiologists blinded to the nature of the lesions. Patient and lesion characteristics were recorded, with a focus on washout on portal venous and/or delayed phases. Lesions were compared using Chi-square, Fisher's, Student's t or Mann-Whitney U tests. RESULTS: A total of 49 patients (mean age 35⯱â¯12â¯years; 34 women [69%] and 15 men [31%]) with 241 benign lesions and 12 HCC lesions were analyzed. Patients with HCC were significantly older (mean age 44⯱â¯16 vs. 33⯱â¯9â¯years, pâ¯=â¯0.005), with higher alpha-fetoprotein (AFP) levels (median 16 vs. 3â¯ng/ml, pâ¯=â¯0.007). Washout was depicted in 9/12 (75%) HCC, and 69/241 (29%) benign lesions (p <0.001). A total of 52/143 (36%) lesions ≥1â¯cm with arterial hyperenhancement showed washout (9 HCC and 43 benign lesions). In this subgroup, the specificity of washout for the diagnosis of HCC was 67%. Adding T1-w hypointensity raised the specificity to 100%. A serum AFP >15â¯ng/ml was associated with 95% specificity. CONCLUSION: Washout was observed in close to one-third of benign lesions, leading to an unacceptably low specificity for the diagnosis of HCC. The non-invasive diagnostic criteria proposed for cirrhotic patients cannot be extrapolated to patients with BCS. LAY SUMMARY: Washout on MRI is depicted in a significant proportion of benign nodules in patients with Budd-Chiari syndrome (BCS), limiting its value for the differentiation between benign and malignant lesions. Criteria proposed for the non-invasive diagnosis of hepatocellular carcinoma in patients with cirrhosis cannot be extrapolated to patients with BCS. Additional imaging findings and patient characteristics, including alpha-fetoprotein serum level, can help determine the probability of a nodule being HCC in patients with BCS.
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Síndrome de Budd-Chiari/diagnóstico por imagem , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Idoso , Síndrome de Budd-Chiari/patologia , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Fígado/patologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem , alfa-Fetoproteínas/análiseRESUMO
BACKGROUND & AIMS: Acute severe ulcerative colitis (ASUC) is a life-threatening condition managed with intravenous steroids followed by infliximab, cyclosporine, or colectomy (for patients with steroid resistance). There are no biomarkers to identify patients most likely to respond to therapy; ineffective medical treatment can delay colectomy and increase morbidity and mortality. We aimed to identify biomarkers of response to medical therapy for patients with ASUC. METHODS: We performed a retrospective analysis of 47 patients with ASUC, well characterized for their responses to steroids, cyclosporine, or infliximab, therapy at 2 centers in France. Fixed colonic biopsies, collected before or within the first 3 days of treatment, were used for microarray analysis of microRNA expression profiles. Deep neural network-based classifiers were used to derive candidate biomarkers for discriminating responders from non-responders to each treatment and to predict which patients would require colectomy. Levels of identified microRNAs were then measured by quantitative PCR analysis in a validation cohort of 29 independent patients-the effectiveness of the classification algorithm was tested on this cohort. RESULTS: A deep neural network-based classifier identified 9 microRNAs plus 5 clinical factors, routinely recorded at time of hospital admission, that associated with responses of patients to treatment. This panel discriminated responders to steroids from non-responders with 93% accuracy (area under the curve, 0.91). We identified 3 algorithms, based on microRNA levels, that identified responders to infliximab vs non-responders (84% accuracy, AUC = 0.82) and responders to cyclosporine vs non-responders (80% accuracy, AUC = 0.79). CONCLUSION: We developed an algorithm that identifies patients with ASUC who respond vs do not respond to first- and second-line treatments, based on microRNA expression profiles in colon tissues.
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Biomarcadores/análise , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo/patologia , Monitoramento de Medicamentos/métodos , Perfilação da Expressão Gênica/métodos , MicroRNAs/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Aprendizado Profundo , Feminino , França , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: To identify treatments likely to prevent progression towards irreversible transmural intestinal necrosis (ITIN) in acute mesenteric ischemia (AMI). METHODS: Prospective observational cohort study from a French intestinal stroke center. Multivariate analysis using a time-dependent Cox regression model. RESULTS: Between 2009 and 2015, 67 patients with AMI were included. ITIN occurred in 34% of patients and mortality was 13%. Oral antibiotics was independently associated with a decreased risk of ITIN (HR: 0.16 (95% CI = 0.03-0.62); p = 0.01). CONCLUSIONS: By decreasing luminal bacterial load and translocation, oral antibiotics in addition to early revascularization might reduce progression of AMI to ITIN.
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Antibacterianos/uso terapêutico , Intestinos/patologia , Isquemia Mesentérica/terapia , Oclusão Vascular Mesentérica/terapia , Administração Oral , Adulto , Idoso , Anticoagulantes/uso terapêutico , Transfusão de Sangue , Estudos de Coortes , Progressão da Doença , Feminino , Hidratação , Humanos , Masculino , Isquemia Mesentérica/patologia , Pessoa de Meia-Idade , Necrose , Modelos de Riscos Proporcionais , Estudos Prospectivos , Inibidores da Bomba de Prótons/uso terapêutico , Procedimentos Cirúrgicos VascularesRESUMO
The formation of tertiary lymphoid organs (TLOs) is orchestrated by the stromal cells of tissues chronically submitted to inflammatory stimuli, in order to uphold specific adaptive immune responses. We have recently shown that the smooth muscle cells of the arterial wall orchestrate the formation of the TLOs associated with atherosclerosis in response to the local release of TNF-α. Observational studies have recently documented the presence of structures resembling TLOs the creeping fat that develops in the mesentery of patients with Crohn's disease (CD), an inflammatory condition combining a complex and as yet not elucidated infectious and autoimmune responses. We have performed a comprehensive analysis of the TLO structures in order to decipher the mechanism leading to their formation in the mesentery of CD patients, and assessed the effect of infectious and/or inflammatory inducers on the potential TLO-organizer functions of adipocytes. Quantitative analysis showed that both T and B memory cells, as well as plasma cells, are enriched in the CD-affected mesentery, as compared with tissue from control subjects. Immunohistochemistry revealed that these cells are concentrated within the creeping fat of CD patients, in the vicinity of transmural lesions; that T and B cells are compartmentalized in clearly distinct areas; that they are supplied by post-capillary high endothelial venules and drained by lymphatic vessels indicating that these nodules are fully mature TLOs. Organ culture showed that mesenteric tissue samples from CD patients contained greater amounts of adipocyte-derived chemokines and the use of the conditioned medium from these cultures in functional assays was able to actively recruit T and B lymphocytes. Finally, the production of chemokines involved in TLO formation by 3T3-L1 adipocytes was directly elicited by a combination of TNF-α and LPS in vitro. We therefore propose a mechanism in which mesenteric adipocyte, through their production of key chemokines in response to inflammatory/bacterial stimuli, may orchestrate the formation of functional TLOs developing in CD-affected mesentery.
Assuntos
Gordura Abdominal/imunologia , Quimiocinas/metabolismo , Doença de Crohn/imunologia , Intestinos/patologia , Linfócitos/imunologia , Mesentério/patologia , Estruturas Linfoides Terciárias/imunologia , Gordura Abdominal/patologia , Adipócitos , Células Cultivadas , Quimiocinas/genética , Estudos de Coortes , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Larva Migrans , Estudos Prospectivos , Estruturas Linfoides Terciárias/patologiaAssuntos
Neoplasias Meníngeas , Meningioma , Neurilemoma , Microambiente Tumoral , Humanos , Meningioma/patologia , Meningioma/genética , Meningioma/imunologia , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/imunologia , Neurilemoma/patologia , Neurilemoma/genética , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Metilação de DNA , Neurofibromatose 2/genética , Neurofibromatose 2/patologia , Feminino , Masculino , Neurofibromatoses/genética , Neurofibromatoses/patologia , Pessoa de Meia-Idade , Adulto , Neurofibromina 2/genética , MultiômicaAssuntos
Neoplasias Gástricas , Proteína GLI1 em Dedos de Zinco , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/diagnóstico , Proteína GLI1 em Dedos de Zinco/genética , Proteína GLI1 em Dedos de Zinco/metabolismo , Rearranjo Gênico , Feminino , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Colonoscopy with pan-chromoendoscopy (CE) is superior to standard colonoscopy in detecting neoplasia in patients with IBD. Performing random biopsies in unsuspicious mucosa after CE remains controversial. METHODS: Consecutive patients with IBD who underwent surveillance colonoscopy using CE were prospectively included. The standardised procedure used CE, performed targeted biopsies or endoscopic resection on suspicious lesions and then quadrant random biopsies every 10â cm. A panel of five expert pathologists reviewed histological slides with dysplasia. Logistic regression model was used to evidence the factors associated with neoplasia in any or in random biopsies. RESULTS: 1000 colonoscopes were performed in 1000 patients (495 UC, 505 Crohn's colitis). In 82 patients, neoplasia was detected from targeted biopsies or removed lesions, and among them dysplasia was detected also by random biopsies in 7 patients. Importantly, in 12 additional patients dysplasia was only detected by random biopsies. Overall, 140 neoplastic sites were found in 94 patients, 112 (80%) from targeted biopsies or removed lesions and 28 (20%) by random biopsies. The yield of neoplasia by random biopsies only was 0.2% per-biopsy (68/31â 865), 1.2% per-colonoscopy (12/1000) but 12.8% per-patient with neoplasia (12/94). Dysplasia detected by random biopsies was associated with a personal history of neoplasia, a tubular appearing colon and the presence of primary sclerosing cholangitis (PSC). CONCLUSIONS: Despite their low yield, random biopsies should be performed in association with CE in patients with IBD with a personal history of neoplasia, concomitant PSC or a tubular colon during colonoscopy. TRIAL REGISTRATION NUMBER: IRB 001508, Paris 7 University.